This project is a study of the forces and interactions which determine the shapes of animal cells and which drive their dynamic mechanical functions. A new biophysical method has been developed to measure the local deformability of adherent cells in culture. A measured force is applied to a probe (2 Mum diameter at the tip) which indents the exposed surface of a a cell to a measured depth (1 Mum). Because the forces which maintain the shape of a cell must resist its deformation, these measurements of deformability provide information about determinants of shape. A principal objective of the project is to investigate the roles of the major components of the cytoskeleton and the extracellular matrix in maintaining and changing cell morphology. Another goal is to develop an interpretive model with which to extract estimates of cellular viscosity and elasticity from the measured deformability. Once these fundamental tasks have been completed, it will then be possible to use this approach to study mechanical consequences of physiological processes which involve cell shape change such as differentiation or transformation. In the long range it should be possible to combine these results with morphological and biochemical information to produce a model for cellular mechanical properties. This kind of mechanical analysis should have both diagnostic and explanatory value in characterizing changes of cell properties due to normal or abnormal processes.